Background: Recent Food and Drug Administration (FDA) warnings and medical association guidelines focus on potential health risks associated with psychotropic medications, suggesting modifications for clinical practice. These types of evidence-based policies can have an important impact on public health and safety. The VA Pharmacy Benefits Management Services (VA PBM), our primary operational partner in this study is responsible for initiating VA responses to FDA warnings. Despite VA PBM's use of several approaches to convey warnings to Veterans Integrated Service Networks (VISNs), VA facilities, and providers, much remains unknown about the multiple contextual and organizational factors influencing responsiveness to these warnings. A better understanding of VA system and provider level responsiveness could lead to developing and sharing best practices and informing future strategies to improve warning adoption, thereby improving patient care and population safety. Objectives: Given that considerable VA facility-level variation exists in psychotropic prescribing practices, the overarching goal of this study is to examine multilevel responses to external warnings regarding psychotropic medications. We seek to understand variation in the adoption of warnings by VISNs, VA facilities, and providers, and the effect of varying levels of pharmacy integration on response to warnings. We will use two examples of recent warnings designed to mitigate risks associated with psychotropic medications: 1) sudden cardiac events associated with high doses of the antidepressant citalopram [Celexa];5,6 and 2) impaired driving associated with zolpidem [Ambien], a sedative hypnotic medication.7,8 In this context, we will address the following three specific aims: Aim 1: To assess and describe PBM and VISN-level responsiveness and variation in responsiveness to warnings regarding psychotropic medications. Aim 2: To assess prescribing patterns before and after warnings regarding psychotropic medications. Aim 3: To understand specific strategies used by facilities and providers with high response to warnings and barriers encountered by facilities and providers with low response to warnings. Methods: Using both qualitative (using theory-driven semi-structured interviews) and quantitative methods (using surveys and administrative data), we will evaluate multiple factors that could influence facility and provider responsiveness to warnings. This study will be the first mixed methods longitudinal study of warnings for psychotropic medications in a large national health system. Aim 1 will detail the processes by which VHA prescribing policies and guidance were developed, how dissemination was accomplished, and perceived barriers and facilitators to adoption across the system, based on semi-structured interviews with national VA PBM leaders and pharmacy leaders at each VISN (N=21). Aim 2 will employ segmented regression techniques using administrative data pre- and post-warning to identify changes in psychotropic medication prescriptions and patient health monitoring in VHA by VISN and facility. Aim 3 will detail processes by which facilities and providers changed practice in response to warnings and PBM dissemination efforts. Interviews will be conducted with facility leaders (pharmacy, primary care, mental health) in Aim 3A, and surveys will be conducted with primary care providers (PCPs), and psychiatrists in Aim 3B, all of whom will be intentionally sampled based on findings from Aims 1 and 2. Methods developed and refined in this project will be applicable to a broad range of policies for mental health treatment and pharmacosurveillance. Anticipated impacts on Veterans Health: This proposal's impact derives from its ability to overcome weaknesses of previous studies by bringing together unprecedented data resources, qualitative and quantitative methods, new applications of organizational theories, and diverse investigator expertise. This work could improve clinical care and patient safety, directly benefiting VA practice and patients.